Dominant role of GABAB2 and Gβγ for GABAB receptor-mediated-ERK1/2/CREB pathway in cerebellar neurons

Autor: Jianfeng Liu, Chanjuan Xu, Federica Bertaso, Philippe Rondard, Fangli Cao, Xueying Zhang, Haijun Tu, Jean-Philippe Pin
Přispěvatelé: College of Life Sciences, Huazhong University of Science and Technology [Wuhan] (HUST), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1), Département de Pharmacologie Moléculaire, Université Montpellier 2 - Sciences et Techniques (UM2), This work was supported by the National Natural Science Foundation of China (Grants No. 30530820, No.30470368) and Hi-Tech Research and Development Program of China (863 project) (Grants No. 2006AA02Z326). H. T was supported by the fund of outstanding thesis from Huazhong University of Science and Technology (D0611), Rondard, Philippe, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2007
Předmět:
MAPK/ERK pathway
Baclofen
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
MESH: Neurons
MESH: gamma-Aminobutyric Acid
GTP-Binding Protein alpha Subunits
Gi-Go
MESH: GTP-Binding Protein beta Subunits
Mice
chemistry.chemical_compound
0302 clinical medicine
Cerebellum
GTP-Binding Protein gamma Subunits
MESH: Animals
Phosphorylation
MESH: Receptors
GABA-B
Cyclic AMP Response Element-Binding Protein
Extracellular Signal-Regulated MAP Kinases
Receptor
MESH: Extracellular Signal-Regulated MAP Kinases
gamma-Aminobutyric Acid
Mitogen-Activated Protein Kinase 1
Neurons
0303 health sciences
Mitogen-Activated Protein Kinase 3
MESH: GTP-Binding Protein alpha Subunits
Gi-Go
GTP-Binding Protein beta Subunits
MESH: Protein Subunits
Cell biology
MESH: Baclofen
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
Neurons and Cognition (q-bio.NC)
MESH: Mitogen-Activated Protein Kinase 3
MESH: Cyclic AMP Response Element-Binding Protein
MESH: Mitogen-Activated Protein Kinase 1
medicine.medical_specialty
G protein
Allosteric regulation
Biology
GABAB receptor
CREB
Cell Line
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
MESH: Mice
030304 developmental biology
MESH: Humans
MESH: Phosphorylation
[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
Cell Biology
MESH: Cerebellum
MESH: Cell Line
Protein Subunits
Endocrinology
Receptors
GABA-B
nervous system
chemistry
Quantitative Biology - Neurons and Cognition
FOS: Biological sciences
biology.protein
MESH: GTP-Binding Protein gamma Subunits
030217 neurology & neurosurgery
Zdroj: Cellular Signalling
Cellular Signalling, Elsevier, 2007, 19 (9), pp.1996-2002. ⟨10.1016/j.cellsig.2007.05.004⟩
Cellular Signalling, 2007, 19 (9), pp.1996-2002. ⟨10.1016/j.cellsig.2007.05.004⟩
ISSN: 0898-6568
DOI: 10.1016/j.cellsig.2007.05.004
Popis: gamma-aminobutyric acid type B (GABA(B)) receptor is an allosteric complex made of two subunits, GABA(B1) and GABA(B2). GABA(B2) plays a major role in the coupling to G protein whereas GABA(B1) binds GABA. It has been shown that GABA(B) receptor activates ERK(1/2) in neurons of the central nervous system, but the molecular mechanisms underlying this event are poorly characterized. Here, we demonstrate that activation of GABA(B) receptor by either GABA or the selective agonist baclofen induces ERK(1/2) phosphorylation in cultured cerebellar granule neurons. We also show that CGP7930, a positive allosteric regulator specific of GABA(B2), alone can induce the phosphorylation of ERK(1/2). PTX, a G(i/o) inhibitor, abolishes both baclofen and CGP7930-mediated-ERK(1/2) phosphorylation. Moreover, both baclofen and CGP7930 induce ERK-dependent CREB phosphorylation. Furthermore, by using LY294002, a PI-3 kinase inhibitor, and a C-term of GRK-2 that has been reported to sequester Gbetagamma subunits, we demonstrate the role of Gbetagamma in GABA(B) receptor-mediated-ERK(1/2) phosphorylation. In conclusion, the activation of GABA(B) receptor leads to ERK(1/2) phosphorylation via the coupling of GABA(B2) to G(i/o) and by releasing Gbetagamma subunits which in turn induce the activation of CREB. These findings suggest a role of GABA(B) receptor in long-term change in the central nervous system.
Databáze: OpenAIRE
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